Fecal Microbiota Transplantation for Kidney Cancer

(PERFORM Trial)

Overseen By Ricardo Fernandes, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: Antibiotics, Immunosuppressants, Steroids

Disqualifiers: Pregnancy, Immunodeficiency, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Fecal Microbiota Transplantation (FMT) can help patients with kidney cancer better tolerate a powerful but toxic combination of immunotherapy drugs, ipilimumab and nivolumab. Although these drugs can effectively combat cancer, they often cause severe side effects, leading to treatment discontinuation. By enhancing gut bacteria diversity through FMT, researchers aim to reduce these side effects, allowing patients to continue their cancer treatment with fewer interruptions. The trial seeks patients with advanced or metastatic kidney cancer who have been diagnosed within the past year and are experiencing significant daily impacts from their condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or antibiotics before the trial. It's best to discuss your specific medications with the trial team.

What prior data suggests that Fecal Microbiota Transplantation is safe for kidney cancer patients?

Research has shown that Fecal Microbiota Transplantation (FMT) is already used to treat recurrent Clostridium difficile infections, achieving success rates between 80% and 90%. This indicates that FMT can be effective and generally safe for certain infections.

However, information on the safety of FMT for treating kidney cancer is limited. Some studies suggest that FMT might help patients better tolerate cancer drugs by improving gut health. Yet, no large, randomized studies have specifically addressed kidney cancer.

As this is an early-phase trial, the primary focus is on safety. Early trials like this one are typically designed to assess how well patients tolerate the treatment. While FMT appears safe for some uses, its safety for kidney cancer patients remains under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for kidney cancer, which typically involve drugs like nivolumab and ipilimumab, fecal microbiota transplantation (FMT) introduces a novel approach by using the gut microbiome to potentially enhance the immune response against cancer. Researchers are excited about FMT because it offers a unique mechanism of action: altering the gut bacteria to improve the effectiveness of existing immunotherapies. This could make the immune system more responsive, potentially leading to better outcomes for patients with kidney cancer.

What evidence suggests that Fecal Microbiota Transplantation is effective for reducing toxicity in kidney cancer treatment?

Studies have shown that Fecal Microbiota Transplantation (FMT) can improve cancer treatment outcomes. In some cases, FMT increased progression-free survival, allowing patients to live longer without their cancer worsening. It alters gut bacteria to support a healthier immune system. Research indicates that FMT might also reduce the side effects of cancer drugs, making them easier to tolerate. This could enable patients to adhere to their treatment plan longer, potentially leading to better results. Participants in this trial will receive FMT combined with the approved standard of care treatment using nivolumab and ipilimumab. ^{1 5 6 7 8}

Who Is on the Research Team?

Saman Maleki, PhD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Ricardo Fernandes, MD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic renal cell carcinoma, specifically those at intermediate or poor risk. Participants must be in good physical condition (KPS ≥70%), able to swallow capsules, and have not had certain prior treatments including systemic therapy for RCC. Pregnant individuals, those with immunodeficiency, chronic intestinal diseases, active infections requiring systemic therapy, or a history of serious autoimmune disease are excluded.

Inclusion Criteria

Understand non-infectious risks associated with FMT administration and that the long term data regarding safety risks of FMT are lacking

Able to provide written informed consent

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

I haven't had radiation for bone metastasis in the last 2 weeks or any radiation in the last 4 weeks.

Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I have not received a live vaccine in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Fecal Microbiota Transplantation

Participants receive Fecal Microbiota Transplantation before the start of immunotherapy and during the first two cycles of ipilimumab treatment

10 weeks

4 visits (in-person)

Immunotherapy Treatment

Participants receive combination treatment with ipilimumab and nivolumab

28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplantation

Trial Overview The study tests if Fecal Microbiota Transplantation (FMT) can reduce the side effects of ipilimumab/nivolumab immunotherapy in kidney cancer patients. The goal is to allow patients to tolerate their cancer treatment better by altering gut bacteria before and during the first two cycles of this powerful but potentially toxic drug combination.

How Is the Trial Designed?

Group I: Fecal Microbiota Transplantation Experimental Treatment 1 Intervention

Fecal microbiota transplantation combined with approved standard of care treatment with nivolumab and ipilimumab.

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Academic Medical Organization of Southwestern Ontario

Collaborator

Trials

17

Recruited

1,600+

Published Research Related to This Trial

A kidney transplant recipient successfully treated recurrent urinary tract infections with fecal microbiota transplantation (FMT), remaining symptom-free after the procedure.

The study highlights the need for further research to understand the underlying mechanisms of how FMT works in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. Biehl, LM., Cruz Aguilar, R., Farowski, F., et al.[2019]

Fecal microbiota transplantation (FMT) is an effective treatment for restoring healthy gut bacteria in patients with disrupted intestinal microbiota, particularly in conditions like Clostridium difficile infection.

The review emphasizes the importance of careful donor selection and proper processing and storage of fecal material to ensure the safety and efficacy of the transplantation procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)]. Iakupova, AA., Abdulkhakov, SR., Safin, AG., et al.[2022]

A study involving 123 patients who underwent fecal microbiota transplantation (FMT) over a median follow-up of 30.3 months showed that FMT has an excellent long-term safety profile, with new medical conditions being unlikely to be related to the procedure.

In patients with recurrent Clostridioides difficile infection, FMT was associated with a significantly higher survival probability compared to those treated with antibiotics, indicating its efficacy in improving long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry. Yau, YK., Lau, LHS., Lui, RNS., et al.[2023]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

Fecal microbiota transplantation (FMT) showed significant long-term efficacy in reducing IBS symptoms, with response rates of 69.1% and 77.8% for the 30g and 60g treatment groups, respectively, at 2 years, and 64.9% and 71.8% at 3 years, compared to only 26.3% in the placebo group.

No long-term adverse events were reported, indicating that FMT is a safe intervention for IBS, with improvements in quality of life and a decrease in dysbiosis index observed in the treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. El-Salhy, M., Winkel, R., Casen, C., et al.[2022]

Fecal microbiota transplantation (FMT) is primarily used to treat gastrointestinal diseases caused by harmful microorganisms, but it is also being explored for conditions like metabolic syndrome, diabetes, cancer, and Parkinson's disease.

The review discusses the effects of FMT on weight gain, immune response, and various diseases, while also addressing potential side effects that recipients may experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in disease therapy. Antushevich, H.[2020]

Fecal microbiota transplantation (FMT) is a therapeutic procedure that involves transferring fecal matter from a healthy donor to treat diseases, particularly recurrent Clostridium difficile infections.

Recent research highlights the importance of the human microbiome, showing that the complex mixture of microorganisms in our bodies plays a crucial role in overall health and disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intestinal microbiota and the efficacy of fecal microbiota transplantation in gastrointestinal disease. Aroniadis, OC., Brandt, LJ.[2022]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Citations

1. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-kidney-cancer/154853-esmo-2024-fecal-microbiota-transplantation-fmt-versus-placebo-in-patients-receiving-pembrolizumab-plus-axitinib-for-metastatic-renal-cell-carcinoma-preliminary-results-of-the-randomized-phase-2-tacito-trial.html

ESMO 2024: Fecal Microbiota Transplantation vs Placebo ... ESMO 2024 Preliminary results from the TACITO trial show fecal microbiota transplantation (FMT) increases progression-free survival in mRCC ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001471

Fecal microbiota transplantation to enhance cancer ... This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10653624/

Gut microbiota and immunotherapy of renal cell carcinoma Fecal microbiota transplantation (FMT) consists in the transfer of ... Efficacy of different faecal microbiota transplantation ...

4. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-04183-y

Microbiota boost immunotherapy? A meta-analysis dives into ... Fecal microbiota transplantation (FMT), which alters the gut microbiome, has shown promise in enhancing ICIs' therapeutic effects. Methods. We ...

5. onclive.com onclive.com/view/fecal-microbiota-transplantation-boosts-response-to-pembrolizumab-plus-axitinib-in-mrcc

Fecal Microbiota Transplantation Boosts Response to ... The addition of fecal microbiota transplantation to pembrolizumab and axitinib raised the efficacy of the combination in metastatic renal cell carcinoma.

6. urotoday.com urotoday.com/video-lectures/advanced-kidney-cancer/video/4288-fecal-microbiota-transplant-boosts-immunotherapy-in-metastatic-renal-cell-carcinoma-in-tacito-ii-trial-chiara-ciccarese.html

Fecal Microbiota Transplant Boosts Immunotherapy in ... Regarding FMT, so fecal microbiota transplantation, there are no randomized or prospective data on RCC, so on kidney cancer. But as of today ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6139215/

A Systematic Review of the Efficacy and Safety of Fecal ... Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04758507

Study Details | NCT04758507 | Fecal Microbiota ... Fecal microbiota transplantation (FMT) is a novel therapeutic option based on the restoration of healthy gut microbiota, and is the most effective therapy for ...